This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. While patients with metastatic cancer usually have a variable response to treatment and time to death, understanding the mechanisms that contribute to the heterogeneity of aggressiveness remains a major issue in effective cancer diagnosis and therapy. Previous studies utilizing a set of magnetic resonance (MR) and optical imaging techniques and histology assays have characterized a panel of human melanoma mouse xenografts spanning a full range of progression to metastasis. Despite the metabolic challenges such as low blood perfusion and presumably nutrition starvation, the aggressive tumor cores contained few apoptotic cells as shown by TUNEL assay. Autophagy promotes the survival of cancer cells under starvation or under conditions of cellular stress. We hypothesize that higher autophagy is associated with more aggressive cancer and autophagy may provide new insight into the mechanisms of cancer metastasis and support the development of novel therapeutic approaches by targeting autophagy.